Dasatinib-Induced Colitis in a Patient with Chronic Myelogenous Leukemia

Colite por Dasatinib em Doente com Leucemia Mieloide Crónica

David N. Perdigoto^a, Sandra Lopes^a, Francisco Portela^a, Maria Augusta Cipriano^b, Luís Tomé^a

^aGastroenterology Department and ^bPathology Department, Coimbra Hospital and University Center, Coimbra, Portugal

^* Corresponding author.

Keywords: Dasatinib, Colitis, Hematochezia, Chronic myelogenous leukemia

A 54-year-old man presented to his doctor with bloody diarrhea (4–8 bowel movements/day) that had lasted for 4 weeks. He also complained about occasional bright red hematochezia. Following this consultation, a bacteriolog­ical and parasitological stool examination was done and was negative. Afterwards, a colonoscopy showed diffuse papular erythematous areas, more severe in the sigmoid colon, and respective biopsies revealed nonspecific coli­tis. He was then scheduled for a gastroenterology ap­pointment and at that time he described improvement of his overall condition and spontaneous resolution of the diarrhea and hematochezia. The patient had a history of chronic myelogenous leukemia (CML), depression, high blood pressure, and obstructive sleep apnea. He was re­ceiving dasatinib for the CML for two and a half years, following a previous imatinib therapy that failed due to drug resistance. Hematological remission had been achieved with dasatinib 2 months prior to the gastroen­terological consultation. A control colonoscopy was per­formed and showed colonic loss of the normal submuco­sal vascular pattern with multiple areas characterized by edema, erythematous and papular lesions associated with erosions, small ulcers, and exudation (Fig. 1). This pat­tern was diffuse throughout the colon but more severe in the descending and sigmoid segments and rectum. The histopathological examination allowed the identification of mild irregular and branched crypts, diffuse lamina pro­pria hemorrhage, and presence of eosinophils, neutro­phils, and some eosinophilic crypt abscesses (Fig. 2). Apoptotic bodies and intraepithelial lymphocytes were absent. Cytomegalovirus infection was excluded with sample immunochemistry staining and Clostridium dif­ficile infection was also excluded due to absence of the pathogenic toxin in a stool analysis. These endoscopic and pathological features are consistent with the diagno­sis of dasatinib-induced colitis (DIC) [1, 2].

 

 

Dasatinib is an oral BCR-ABL tyrosine kinase inhibi­tor that is indicated for CML treatment, particularly after development of imatinib resistance. Dasatinib has several side effects and gastrointestinal hemorrhage has been re­ported to occur in 2–9% cases. Although well described in the literature [3–5], DIC is a less common side effect.

The typical presentation is characterized by bloody di­arrhea that usually follows weeks to months after the ini­tiation of dasatinib but can also occur several years after treatment. In the majority of cases, the drug therapy needs to be interrupted because of permanent or severe symptoms. Other options are to reduce the drug dose or switch to another tyrosine kinase inhibitor such as nilo­tinib [2]. In this case, a multidisciplinary meeting was made and the decision was to maintain the treatment be­cause the patient did not develop symptomatic relapse, confirmed with two subsequent colonoscopies, executed during gastroenterological follow-up, that showed signif­icant improvement in the mucosal lesions. Additionally, the patient had been shown to be resistant to imatinib and the consequences from withdrawing dasatinib could jeopardize the patient’s hematological and global health status.

The endoscopic DIC pattern can be misleading. There­fore, it is important to keep in mind that colitis presenting with bloody diarrhea is an uncommon but possible com­plication of dasatinib treatment. Infectious conditions must be ruled out, mainly cytomegalovirus infection, which can occur simultaneously.

 

]]> References

1 Ahn H, Kwon J, Sohn S, Kwon J, Kim J, Yoon SS, et al: A case of dasatinib-induced hemor­rhagic colitis diagnosed by the lymphocyte transformation test in a chronic myeloid leu­kemia patient. Indian J Hematol Blood Trans­fus 2016;32:96–99.         [ Links ]

2 Chisti M, Khachani A, Brahmanday G, Klam­erus J: Dasatinib-induced haemorrhagic coli­tis in chronic myeloid leukaemia (CML) in blast crisis. BMJ Case Rep 2013–200610.         [ Links ]

3 Nishiwaki S, Maeda M, Yamada M, et al: Clin­ical efficacy of fecal occult blood test and colo­noscopy for dasatinib-induced hemorrhagic colitis in CML patients. Blood 2017;129:126–128.         [ Links ]

4 Shanshal M, Shakespeare A, Thirumala S, Fenton B, Quick DP: Dasatinib-induced T-cell-mediated colitis: a case report and review of the literature. Acta Haematol 2016;136:219–228.         [ Links ]

5 Yim E, Choi YG, Nam YJ, Lee J, Kim JA: Da­satinib induces severe hemorrhagic colitis in a patient with accelerated phase of chronic myelogenous leukemia. Korean J Intern Med 2016, Epub ahead of print.         [ Links ]

Statement of Ethics

As this is a short case report of endoscopic nature (Endoscopic Snapshot), approval from the institutional ethics commission was not necessary. The patient authorized the publication of the data and the patient’s anonymity is preserved in the article.

Disclosure Statement

The authors declare no conflicts of interest.

^* Corresponding author.

Dr. David N. Perdigoto

Gastroenterology Department, Coimbra Hospital and University Center

PT–3000-075 Coimbra (Portugal)

E-Mail davidperdigoto@gmail.com

Received: July 6, 2017; Accepted after revision: August 22, 2017

Author Contributions

David N. Perdigoto: data acquisition and editing, manuscript drafting. Sandra Lopes: data acquisition and manuscript revision. Maria Augusta Cipriano: pathological editing and manuscript re­vision. Francisco Portela, Luís Tomé: manuscript revision.